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The Anti-HIV Activity of Entecavir: Serum HIV RNA Decreases and Selection of the M184V Mutation Occurs in both ART-naïve and -experienced HIV/HBV-co-infected Individuals
Jennifer Audsley*1,2,3, J Sasadeusz1,3, A Mijch1,2, R Baden4, J Caro4,5, H Hunter6, G Matthews7, S Olender8, S Lewin1,2,3, and C Thio9
1Alfred Hosp, Melbourne, Australia; 2Monash Univ, Melbourne, Australia; 3CCREID, Univ of Melbourne, Australia; 4Harvard Med Sch, Boston, MA, US; 5Fenway Community Hlth, Boston, MA, US; 6AID Atlanta, GA, US; 7Natl Ctr in HIV Epi and Clin Res, Sydney, Australia; 8Columbia Univ Med Ctr, New York, NY, US; and 9Johns Hopkins Univ Sch of Med, Baltimore, MD, US
Background: Entecavir (ETV), a guanosine analogue approved
for the treatment of chronic hepatitis B, was previously recommended in
multiple guidelines as an agent for hepatitis B virus (HBV) treatment in HIV/HBV-co-infected
individuals when ART was not indicated. However, we recently demonstrated that
ETV has in vitro and in vivo anti-HIV activity. To further
characterize the anti-HIV activity of ETV and determine the risk factors
associated with development of the HIV polymerase mutation M184V, we established
a multi-center, international cohort study of HIV/HBV-co-infected individuals
who had received ETV in the absence of other antiretroviral agents.
Methods: In Australia and the United States, 17 HIV/HBV-co-infected
individuals who received ETV monotherapy were identified at multiple sites. HIV
RNA and HBV DNA levels, HIV polymerase sequencing and other clinical data were
abstracted from medical records prior to receiving (earliest data July 2004)
and while on ETV monotherapy (until July 2007).
Results: Of this group, 10 were ART-naive and 7 were
ART-experienced. Naive individuals had a median HIV RNA reduction of 1.0 log10
(range 0.5 to 2.0) after a median of 113 days of ETV (range 17 to 291). The
experienced individuals had a median HIV RNA reduction of 1.1 log10 (range
0.1 to 2.3) after a median of 96 days of ETV (range 75 to 215). Of 17 people, 12
(71%) demonstrated a reduction of 0.5 log10 or greater, including 7
of the 10 naive persons (70%) and 5 of the 7 experienced individuals (71%); 4
individuals (24%) also had a rebound of HIV viral load of 0.5 log10
or greater after achieving their nadir HIV RNA. Polymerase sequencing was
confirmed for 12 of the cohort (8 naive and 4 experienced), of whom 3 naive and
3 experienced individuals selected the M184V mutation. Statistically
significant risk factors for selection of the M184V mutation by univariate
analysis were reduction in HBV viral load (p = 0.024) and total duration
of ETV monotherapy (p = 0.045). All 3 treatment experienced individuals
who selected the M184V had previous lamivudine treatment.
Conclusions: ETV monotherapy results in a clinically
significant reduction in HIV RNA in the majority but not all HIV/HBV-co-infected
individuals and can select for the M184V mutation, even in HIV treatment naive
individuals. HIV/HBV-co-infected individuals should not receive ETV
monotherapy.
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